One of the most confounding endocrine emergencies in history, thyroid storm is no longer a death sentence. Here’s a look at what’s new on the horizon in the prevention, recognition, and treatment of this once fatal malady.
Once approaching 100% mortality only a century ago, thyroid storm remains one of the most life-threating endocrine emergencies at a 10% to 20% mortality rate even with advances in prevention, recognition, and treatment. Though rare, the confluence of circumstances that aggravates thyrotoxicosis so drastically leaves devastation in its wake, failing prompt treatment.
Chasing the storm
Accounting for the persistently high mortality rate is that multiple body systems are pushed beyond their ability to compensate for the existing high thyroid hormone (TH) level. “Each of the features of uncomplicated hyperthyroidism is exaggerated to an extreme in thyroid storm, leaving not a second to lose,” says Colonel Henry B. Burch, MD, professor of medicine and chair of the Endocrinology Division of the Uniformed Services University of the Health Sciences, in Bethesda, Md., endocrinology consultant to the Office of the U.S. Army Surgeon General, and Endocrinology Service at the Walter Reed National Military Medical Center, in Bethesda.
The definitive cause, however, remains elusive. “Our best clue is a list of known precipitants associated with a sudden increase in thyroid hormone in the circulation,” Burch says (see box, p. 12). “Therefore, the key to survival is making the diagnosis.”
Making the diagnosis is not quite so straightforward, however. Patients can present with symptoms of sepsis, stimulant intoxication, or coma; go undiagnosed and, therefore, untreated; and die from multisystem decompensation. To further complicate diagnosis, there is no such thing as the “typical patient.” Although universally accepted criteria do not exist for diagnosing thyroid storm, in 1993, Burch and colleague Leonard Wartofsky, MD, professor of medicine, Georgetown University School of Medicine and editor-in-chief of the Journal of Clinical Endocrinology & Metabolism, introduced the empirically derived, BurchWartofsky-Point-Scale (BWPS) to assess the likelihood of thyroid storm based on quantitative clinical criteria.
Yet even a single day for the clinician to arrive at the diagnosis can be too late. “You need a good clinical indication,” Burch says. These include signs of systemic decompensation, such as cardiovascular dysfunction (e.g., congestive heart failure, cardiomyopathy, cerebrovascular accident, pulmonary thromboembolism) gastrointestinal (GI) dysfunction, and central nervous system (CNS) disturbance (e.g., anxiety, psychosis, global hyperkinesis), in addition to signs and symptoms of hyperthyroidism, such as high temperature, tachycardia, hyperdefecation, and a high TH level. “Then you throw everything you’ve got in your arsenal at it.”
However, making the diagnosis is by no means simply a matter of a TH level increased beyond what constitutes hyperthyroidism or thyrotoxicosis. In fact, the BWPS awards a score independently from TH level. “It’s not a level—it’s a patient’s ability to compensate,” says Stephanie L. Lee, MD, PhD, director of the Thyroid Health Center of the Boston Medical Center, and associate professor of Medicine at Boston University School of Medicine. The degree of excess TH is not necessarily more profound than that seen in uncomplicated thyrotoxicosis, but a catalyst, such as infection or childbirth, causes the patient to decompensate and tip over into thyroid storm. “The diagnosis is clinical, based on the presence of a known precipitant plus thermodynamic dysregulation and cardiovascular, CNS, and GI dysfunction,” Lee says, “and a key point is that the fever is out of context with any existing infection.”
In 2012, Takashi Akamizu, MD, PhD, of Wakayama Medical University, Japan, and the Japanese Thyroid Association (JTA), introduced a qualitative diagnostic system. “Diagnostic Criteria, Clinical Features, and Incidence of Thyroid Storm Based on Nationwide Surveys” published recently in Thyroid, was the largest case series of thyroid storm conducted to date, comprising retrospective analysis of 282 definite and 74 suspected cases from 2004 to 2008. Their system grades thyroid storm based on the existence of one or more of the five BWPS diagnostic criteria plus thyrotoxicosis. TS1 (definite) includes CNS plus one other manifestation or three manifestations other than CNS. TS2 (suspected) includes two manifestations other than CNS or history of thyroid disease, presents with exophthalmos and goiter, and meets either of the criteria for definite cases.
“The JTA system was also largely empirically derived and includes features that mirror those in the BWPS,” Burch says. The difference lies in its sensitivity. “The JTA system may result in the selection of a slightly smaller group of patients for aggressive therapy,” Burch adds. However, the finer point remains that thyroid storm is not simply a matter of TH level — it’s a much more complicated clinical picture and a more complex etiology. Therefore, the two diagnostic systems may work most effectively in tandem. “There was a significant correlation between our diagnostic criteria and the BWPS, suggesting that both the BWPS and our criteria are helpful in diagnosing thyroid storm,” Akamizu says. “As the next obvious step, therapeutic procedures that aim for a better prognosis should be created.”
Weathering the Storm
Catching thyroid storm in the impending stage promotes the best chance of patient survival. The treatment approach is three-pronged: 1) make the diagnosis sufficiently early; 2) determine etiology and treat to reverse (e.g., antibiotics for infection); and 3) resuscitate and initiate supportive care (e.g., antipyretics, fluids, nutrition, telemetry, invasive monitoring), all of which happens concurrently. “Then there are caveats that make medical treatment very complicated,” Lee says. Reducing the TH concentration and preventing its peripheral actions must happen (optimally within 48 hours), as clinicians have known since the 1920s, but treating with iodine, which blocks both synthesis and release, can only be done at least one hour after antithyroid drug (ATD) therapy has been instituted. Propylthiouracil (PTU) blocks the synthesis of thyroid hormones and inhibits the peripheral conversion of T4 to T3, but because of the risks associated with PTU, “you have to balance how severely T3 toxic the patient is with how severely they are decompensating, and then switch to a safer drug, such as methimazole,” Lee explains. Because the thyroid gland is unique in that it stores pre-formed TH, blocking synthesis is not enough to eliminate the excess TH; therefore, iodine must also be given. β-Blockers (e.g., propranolol) treat target organ effects. If this combination of drugs is unsuccessful in lowering thyroid hormone levels, dialysis and plasmapheresis can be undertaken as a last resort—“when your back is against the wall,” Lee adds.
Another possible complication to watch for can result from cooling the extremely hyperthermic patient with blankets or alcohol baths, which paradoxically can raise the temperature if the patient starts to shiver, Lee says.
With proper treatment, improvement is generally seen within two days, and full recovery is seen in one week. “Then plan for definitive therapy,” Burch says. “Once the patient is euthyroid, institute radioiodine or thyroidectomy, noting that with radioiodine, iodine given during treatment of thyroid storm must be cleared over several weeks.”
Two vital points for clinicians are to educate patients and to avoid precipitants. “Patients should be alert for fever or confusion, and clinicians should avoid abrupt ATD discontinuation (unless there is a major adverse drug effect), pretreat high-risk patients with ATDs before radioiodine therapy, and avoid surgery in thyrotoxic patients — completely correct thyrotoxicosis before elective surgery,” Burch says.
With the mortality rate still so relatively high, this confounding syndrome warrants continued research into effective treatment. As experts agree, early detection is critical, but with the physiologic complexity that thyroid storm entails, early detection may not always suffice.
— Horvath is a freelance writer based in Baltimore, Md. She wrote about childhood obesity in the July issue